In convection-enhanced delivery (CED), drugs are infused locally into tissue through a cannula inserted into the tissue. Transport of the infused material is dominated by convection, which enhances drug penetration into a target tissue compared with diffusion-mediated delivery or systemic delivery.
CED has emerged as a leading investigational delivery technique for the treatment of several disorders. For example, one of the fundamental barriers to treatment of chronic neuropathological conditions is the Blood-Brain-Barrier (BBB). The BBB protects the brain by very selectively allowing only molecules of very small size and that are soluble in fat. Larger molecule drugs that have the potential to cure patients with neurological disorders cannot cross the BBB. Direct targeted intraparenchymal injection and/or via CED can be used to bypass the blood-brain barrier by infusing compounds through a needle, cannula, or microcatheter directly into brain parenchyma or a brain tumor. Clinical trials using existing devices show mixed results and suggest that the outcome of the therapy depends strongly on the extent of penetration and distribution of the drug into the brain, which is determined by infusion velocity, the relative rates of convection and elimination during CED, and various properties of the target tissue.
To increase the infusion velocity, flexible microcatheter designs have been constructed to reduce backflow of the drug-containing fluid between the tissue and needle-shaft interface. To reduce the elimination rate and thereby extend the penetration distance, infused compounds have been incorporated into nanoparticles such as liposomes or polymeric beads, which protect the compounds during transport. However, backflow of drug during CED treatment still remains a critical problem in clinical practice and the transport of nanoparticles through the brain is hindered, because the size of the nanoparticles is comparable to the size of a typical “pore” of the extracellular space. In addition, the poroelastic nature of the brain tissue contributes to backflow or reflux. Furthermore, it can be difficult to control the spatial distribution of infused molecules and nanoparticles when tissue characteristics vary within the treatment region, such as in heterogeneous tissue and near white matter tracts in the brain. There is therefore a need for improved CED devices, e.g., CED devices with increased penetration distance and/or increased control over the spatial distribution of the infused drug.